The key role of UVA-light induced oxidative stress in human Xeroderma Pigmentosum Variant cells.
Free Radic Biol Med
; 131: 432-442, 2019 02 01.
Article
en En
| MEDLINE
| ID: mdl-30553972
ABSTRACT
The UVA component of sunlight induces DNA damage, which are basically responsible for skin cancer formation. Xeroderma Pigmentosum Variant (XP-V) patients are defective in the DNA polymerase pol eta that promotes translesion synthesis after sunlight-induced DNA damage, implying in a clinical phenotype of increased frequency of skin cancer. However, the role of UVA-light in the carcinogenesis of these patients is not completely understood. The goal of this work was to characterize UVA-induced DNA damage and the consequences to XP-V cells, compared to complemented cells. DNA damage were induced in both cells by UVA, but lesion removal was particularly affected in XP-V cells, possibly due to the oxidation of DNA repair proteins, as indicated by the increase of carbonylated proteins. Moreover, UVA irradiation promoted replication fork stalling and cell cycle arrest in the S-phase for XP-V cells. Interestingly, when cells were treated with the antioxidant N-acetylcysteine, all these deleterious effects were consistently reverted, revealing the role of oxidative stress in these processes. Together, these results strongly indicate the crucial role of oxidative stress in UVA-induced cytotoxicity and are of interest for the protection of XP-V patients.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rayos Ultravioleta
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Reparación del ADN
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Puntos de Control de la Fase S del Ciclo Celular
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Fibroblastos
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article